SR2211

**SR2211** is a potent, selective synthetic small molecule inverse agonist of retinoic acid receptor-related orphan receptor gamma (**RORγ**, also known as RORγt in its isoform), with a binding affinity (Ki) of 105 nM and IC50 of approximately 320 nM for transcriptional repression. Developed through modifications to the dual RORα/γ inverse agonist SR1001 scaffold to enhance RORγ selectivity while minimizing off-target activity on RORα, LXR, and FXR, it potently inhibits IL-17 gene expression and protein production in Th17 cells and EL-4 T lymphocytes, suppresses Th17 differentiation without affecting Th1 pathways, and reduces proinflammatory cytokines (e.g., IL-6, TNF, IL-1β) in macrophages. Demonstrated efficacy in preclinical models including collagen-induced arthritis (CIA) in mice, where oral dosing (up to 20 mg/kg BID) reduced joint inflammation, clinical scores, bone/cartilage erosion, and thymic T-cell populations; also ameliorates mechanical hypersensitivity via spinal microglial suppression, diabetic retinopathy vasculopathy by restoring Treg/Th17 balance, and promotes myelination in oligodendrocyte models. No evidence of clinical advancement; primarily a research tool compound (CAS 1359164-11-6).[1][2][3][5]